In the attempt to determine how an altered phenotype is generated in the process of malignant transformation, analysis will be made of the mechanisms of the acute inhibition of rat liver nuclear RNA synthesis by three potent hepatic carcinogens, acetylaminofluorene (AAF), dimethylnitrosamine (DMN), and ethionine. The aim is to determine if the inhibition of RNA synthesis, in vitro and then in vivo, is accompanied by qualitative changes in the pattern of RNA molecules transcribed, and to relate such changes to the mechanisms of inhibition of RNA synthesis. Preliminary studies have shown inhibition of the template activity of chromatin by DMN and decreased activity of the RNA polymerases solubilized and partially purified from rat liver nuclei treated in vivo with AAF and ethionine. These studies further purification of the altered polymerases. The in vitro and in vivo synthesized RNA's will be compared by fingerprinting techniques and RNA- DNA hybridization. The results of these studies will then be applied to the effect of dietary regimens of the carcinogens.